circTP63-N suppresses the proliferation and metastasis of nasopharyngeal carcinoma via engaging with HSP90AB1 to modulate the YAP1/Hippo signaling pathway  

作　　者：Dan Wang Sicheng Zuo Junshang Ge Hongke Qu Jie Wu Na Yi Lei Shi Yumin Wang Yongzhen Mo Chunmei Fan Yi He Pan Chen Ming Zhou Bo Xiang Wei Xiong Wenjia Guo Zhaoyang Zeng Can Guo 

机构地区：[1]NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism,Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Changsha 410078,China [2]Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education,Cancer Research Institute and School of Basic Medicine Sciences,Central South University,Changsha 410078,China [3]Furong Laboratory,Changsha 410078,China [4]Cancer Research Institute,Affiliated Cancer Hospital of Xinjiang Medical University,Urumqi 830011,China [5]Xinjiang Key Laboratory of Translational Biomedical Engineering,Urumqi 830011,China

出　　处：《Science China(Life Sciences)》2025年第3期689-705,共17页中国科学(生命科学英文版)

基　　金：supported by the National Natural Science Foundation of China(82273174,82072374);the Key Research and Development Program of Hunan Province(2023DK2001,2023SK2004,2023ZJ1120-2);the China Postdoctoral Science Foundation(2024M763705);Key R&D Program in Xinjiang Uygur Autonomous Region(2022B03019-4).

摘　　要：Circular RNAs(circRNAs)play pivotal roles in the development and progression of various diseases,including malignant tumors.However,the biological functions and the underlying mechanisms of many circRNAs remain elusive.In this study,we identified a novel circRNA,circTP63-N,generated through the splicing of exons 2–4 of the TP63 gene in nasopharyngeal carcinoma(NPC).circTP63-N was found to be downregulated in clinical samples of NPC.Both in vitro and in vivo experiments unequivocally demonstrated that circTP63-N inhibits the proliferation and metastasis of NPC cells.Further investigations revealed that circTP63-N interacted with the HSP90AB1 protein,leading to the recruitment of LATS/YAP1 proteins.This,in turn,induced phosphorylation and ubiquitination-dependent degradation of YAP1,resulting in reduced nuclear translocation of YAP1 and inhibition of the transcriptional activation of downstream oncogenic genes,including INHBA,MMP3,and CCNE2.Our findings highlight the identification of circTP63-N,a novel circRNA encoded by an important tumor-relevant gene TP63 and elucidate its molecular mechanism as a tumor suppressor in NPC.These insights offer novel potential molecular markers and therapeutic targets for the clinical diagnosis and treatment of NPC.

关 键 词：nasopharyngeal carcinoma circTP63-N HSP90AB1 YAP1/Hippo signaling pathway PROLIFERATION METASTASIS 

分 类 号：R739.63[医药卫生—肿瘤]